tbuckley/cabot-search huggingface dataset:
Effectiveness of Opioid Analgesic Medicines Prescribed in or at Discharge From Emergency Departments for Musculoskeletal Pain
Authors: Caitlin M.P. Jones, Chung-Wei Christine Lin, Masoud Jamshidi, Christina Abdel Shaheed, Christopher G. Maher, Ian A. Harris, Asad E. Patanwala, Michael Dinh, Stephanie Mathieson
Journal: Annals of Internal Medicine (2022)

The comparative benefits and harms of opioids for musculoskeletal pain in the emergency department (ED) are uncertain.To evaluate the comparative effectiveness and harms of opioids for musculoskeletal pain in the ED setting.Electronic databases and registries from inception to 7 February 2022.Randomized controlled trials of any opioid analgesic compared with placebo or a nonopioid analgesic administered or prescribed to adults in or on discharge from the ED.Pain and disability were rated on a scale of 0 to 100 and pooled using a random-effects model. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework.Forty-two articles were included (n = 6128). In the ED, opioids were statistically but not clinically more effective in reducing pain in the short term (about 2 hours) than placebo and paracetamol (acetaminophen) but were not clinically or statistically more effective than nonsteroidal anti-inflammatory drugs (NSAIDs) or local or systemic anesthetics. Opioids may carry higher risk for harms than placebo, paracetamol, or NSAIDs, although evidence is very uncertain. There was no evidence of difference in harms associated with local or systemic anesthetics.Low or very low GRADE ratings for some outcomes, unexplained heterogeneity, and little information on long-term outcomes.The risk-benefit balance of opioids versus placebo, paracetamol, NSAIDs, and local or systemic anesthetics is uncertain. Opioids may have equivalent pain outcomes compared with NSAIDs, but evidence on comparisons of harms is very uncertain and heterogeneous. Although factors such as route of administration or dosage may explain some heterogeneity, more work is needed to identify which subgroups will have a more favorable benefit-risk balance for one analgesic over another. Longer-term pain management once dose thresholds are reached is also uncertain.None. (PROSPERO: CRD42021275293).
Pancreatic duct stenting by the rendezvous technique from the minor to major papilla for severe pancreatitis due to papillary stenosis after endoscopic papillectomy
Authors: Shota Harai, Mitsuharu Fukasawa, Yoshimitsu Fukasawa, Shinichi Takano, Nobuyuki Enomoto
Journal: Endoscopy (2022)

A pancreatic duct (PD) stent placement after endoscopic papillectomy (EP) is recommended to prevent papillary stenosis [1]. However, there are cases in which pancreatitis due to papillary stenosis develops after stent removal, making endoscopic PD drainage difficult [2] [3].
Continuation of common bile duct clearance with gallbladder stenting after duodenal perforation with subsequent treatment for tension pneumoperitoneum and pneumothorax
Authors: Natee Faknak, Santi Kulpatcharapong, Salin Samutrangsi, Parit Mekaroonkamol, Wiriyaporn Ridtitid, Rungsun Rerknimitr
Journal: Endoscopy (2022)

An 88-year-old woman underwent endoscopic retrograde cholangiopancreatography (ERCP) because of septic cholangitis with acute calculous cholecystitis. Unfortunately, incidental duodenal perforation (Stapfer classification type 1) [1] occurred during duodenoscope intubation by our trainee endoscopist. Gastroscopy with a transparent cap revealed a linear 4-cm defect with active oozing at the duodenal apex ([Video 1]). Perforation closure was attempted with preceding guidewire insertion into the downstream duodenal lumen ([Fig. 1]) to prevent accidental luminal closure [2]. The first traumatic type over-the-scope clip (OTSC, 12/6t; Ovesco) was deployed by suction on the lacerating tissue at the caudal side of the defect ([Fig. 2]). However, the defect did not close completely; therefore, a second OTS clip was deployed using twin graspers to appose the edges of the defect. Contrast enterography revealed no intraperitoneal leakage ([Fig. 3]). Immediately after closure, ERCP with stones removal and transpapillary gallbladder stenting with a double-pigtail plastic stent to prevent recurrent cholecystitis was successfully performed. At almost 40 minutes before completion of the procedure, the patient developed marked abdominal distension, hypotension, and desaturation. Tension pneumoperitoneum with right pneumothorax was confirmed by fluoroscopy ([Fig. 4]). Emergency needle decompression was performed using an 18 G needle to release the tension pneumoperitoneum, and the patient was then intubated. Her abdomen gradually softened with an improvement in oxygen saturation. At 4 hours later, plain radiography showed no free air ([Fig. 5]). The patient was extubated and resumed oral intake the following day.
The Significance of Hypothalamic Inflammation and Gliosis for the Pathogenesis of Obesity in Humans
Authors: Leticia E Sewaybricker, Alyssa Huang, Suchitra Chandrasekaran, Susan J Melhorn, Ellen A Schur
Journal: Endocrine Reviews (2022)

Abstract Accumulated preclinical literature demonstrates that hypothalamic inflammation and gliosis are underlying causal components of diet-induced obesity in rodent models. This review summarizes and synthesizes available translational data to better understand the applicability of preclinical findings to human obesity and its comorbidities. The published literature in humans includes histopathologic analyses performed postmortem and in vivo neuroimaging studies measuring indirect markers of hypothalamic tissue microstructure. Both support the presence of hypothalamic inflammation and gliosis in children and adults with obesity. Findings predominantly point to tissue changes in the region of the arcuate nucleus of the hypothalamus, although findings of altered tissue characteristics in whole hypothalamus or other hypothalamic regions also emerged. Moreover, the severity of hypothalamic inflammation and gliosis has been related to comorbid conditions, including glucose intolerance, insulin resistance, type 2 diabetes, and low testosterone levels in men, independent of elevated body adiposity. Cross-sectional findings are augmented by a small number of prospective studies suggesting that a greater degree of hypothalamic inflammation and gliosis may predict adiposity gain and worsening insulin sensitivity in susceptible individuals. In conclusion, existing human studies corroborate a large preclinical literature demonstrating that hypothalamic neuroinflammatory responses play a role in obesity pathogenesis. Extensive or permanent hypothalamic tissue remodeling may negatively affect the function of neuroendocrine regulatory circuits and promote the development and maintenance of elevated body weight in obesity and/or comorbid endocrine disorders.
Can you use art to restore the health of a community?
Authors: Richard Smith
Journal: BMJ (2022)

Inhaled steroids are frequently used in childhood asthma, but concerns based on limited objective evidence remain, regarding long-term side-effects. In this study the systemic effects of standard doses of inhaled steroids in childhood asthma were assessed, comparing beclomethasone dipropionate (BDP) with fluticasone propionate (FP). The study was prospective, randomized and double-blind. Twenty-three steroid-naive children with moderately severe asthma, aged 5-10 yrs, were allocated either BDP (400 microg x day(-1) or FP (200 microg x day(-1)) using a metered-dose inhaler with a spacer. Asthma control was assessed at regular intervals over 20 months. Fasting morning blood and overnight urine samples were collected for estimation of serum cortisol, serum 1-carboxyterminal telopeptide (ICTP), serum osteocalcin and urine deoxypyridinoline (DPD). Bone mineral density (BMD) was measured at each visit. None of the markers of bone turnover showed any change during the study period. BMD increased at normal rates with age. Serum cortisol significantly decreased on BDP, but not on FP. A significant difference in growth rates was found between the groups, with a slower rate of growth towards the end of the observation period in the BDP group. In conclusion when taken in a relatively modest dose over a period of time, beclomethasone dipropionate had significant effects on the hypothalamic-pituitary-adrenal axis and statural growth in childhood asthma. These systemic effects were not seen with an equipotent dose of fluticasone propionate.
The synthetic lethality of targeting cell cycle checkpoints and PARPs in cancer treatment
Authors: Shuangying Li, Liangliang Wang, Yuanyuan Wang, Changyi Zhang, Zhenya Hong, Zhiqiang Han
Journal: Journal of Hematology & Oncology (2022)

Abstract Continuous cell division is a hallmark of cancer, and the underlying mechanism is tumor genomics instability. Cell cycle checkpoints are critical for enabling an orderly cell cycle and maintaining genome stability during cell division. Based on their distinct functions in cell cycle control, cell cycle checkpoints are classified into two groups: DNA damage checkpoints and DNA replication stress checkpoints. The DNA damage checkpoints (ATM-CHK2-p53) primarily monitor genetic errors and arrest cell cycle progression to facilitate DNA repair. Unfortunately, genes involved in DNA damage checkpoints are frequently mutated in human malignancies. In contrast, genes associated with DNA replication stress checkpoints (ATR-CHK1-WEE1) are rarely mutated in tumors, and cancer cells are highly dependent on these genes to prevent replication catastrophe and secure genome integrity. At present, poly (ADP-ribose) polymerase inhibitors (PARPi) operate through “synthetic lethality” mechanism with mutant DNA repair pathways genes in cancer cells. However, an increasing number of patients are acquiring PARP inhibitor resistance after prolonged treatment. Recent work suggests that a combination therapy of targeting cell cycle checkpoints and PARPs act synergistically to increase the number of DNA errors, compromise the DNA repair machinery, and disrupt the cell cycle, thereby increasing the death rate of cancer cells with DNA repair deficiency or PARP inhibitor resistance. We highlight a combinational strategy involving PARP inhibitors and inhibition of two major cell cycle checkpoint pathways, ATM-CHK2-TP53 and ATR-CHK1-WEE1. The biological functions, resistance mechanisms against PARP inhibitors, advances in preclinical research, and clinical trials are also reviewed.
Widespread Gene Expression Divergence in Butterfly Sensory Tissues Plays a Fundamental Role During Reproductive Isolation and Speciation
Authors: Ningning Wu, Elizabeth Evans, Bas van Schooten, Jesyka Meléndez-Rosa, Yadira Ortiz, Silvia M Planas Soto-Navarro, Steven M Van Belleghem, Brian A Counterman, Riccardo Papa, Wei Zhang
Journal: Molecular Biology and Evolution (2022)

Neotropical Heliconius butterflies are well known for their intricate behaviors and multiple instances of incipient speciation. Chemosensing plays a fundamental role in the life history of these groups of butterflies and in the establishment of reproductive isolation. However, chemical communication involves synergistic sensory and accessory functions, and it remains challenging to investigate the molecular mechanisms underlying behavioral differences. Here, we examine the gene expression profiles and genomic divergence of three sensory tissues (antennae, legs, and mouthparts) between sexes (females and males) and life stages (different adult stages) in two hybridizing butterflies, Heliconius melpomene and Heliconius cydno. By integrating comparative transcriptomic and population genomic approaches, we found evidence of widespread gene expression divergence, supporting a crucial role of sensory tissues in the establishment of species barriers. We also show that sensory diversification increases in a manner consistent with evolutionary divergence based on comparison with the more distantly related species Heliconius charithonia. The findings of our study strongly support the unique chemosensory function of antennae in all three species, the importance of the Z chromosome in interspecific divergence, and the nonnegligible role of nonchemosensory genes in the divergence of chemosensory tissues. Collectively, our results provide a genome-wide illustration of diversification in the chemosensory system under incomplete reproductive isolation, revealing strong molecular separation in the early stage of speciation. Here, we provide a unique perspective and relevant view of the genetic architecture (sensory and accessory functions) of chemosensing beyond the classic chemosensory gene families, leading to a better understanding of the magnitude and complexity of molecular changes in sensory tissues that contribute to the establishment of reproductive isolation and speciation.
ZIF@VO<sub>2</sub> as an Intelligent Nano‐Reactor for On‐Demand Angiogenesis and Disinfection
Authors: Tiejun Yuan, Hui Wang, Minhong Tan, Yang Xu, Qiyao Xiao, Chen Wu, Lihua Peng
Journal: Advanced Healthcare Materials (2022)

Abstract Absent angiogenesis and bacterial infection are two major challenges that simultaneously delay the repair of injured tissues and organs. However, most current therapeutic systems deliver therapeutic cues in a separate and inaccurate manner which stimulates angiogenesis or inhibits infection leading to limited repair and side effects. Advanced therapeutic systems capable of providing accurate angiogenic stimulation and anti‐infection signals in response to the changing microenvironment are urgently needed. Herein, a nano‐reactor (ZFVO) involving zeolitic imidazolate framework‐67 (ZIF‐67)‐deposited hollow vanadium oxide (VO 2 ) is developed to intelligently execute pro‐angiogenesis and/or disinfection via the responsive release of cobalt ions and hydroxyl radicals to the injury and infection sites, respectively. ZFVO nano‐reactor demonstrates a novel strategy for constructing drug‐free nano‐platforms with a hierarchical structure which has potential for the accurate treatment of trauma and orthopedic diseases.
Empagliflozin Inhibits Cardiac Late Sodium Current by Ca/Calmodulin-Dependent Kinase II
Authors: Julian Mustroph, Maria J. Baier, Steffen Pabel, Thea Stehle, Maximilian Trum, Zdenek Provaznik, Peter J. Mohler, Hassan Musa, Thomas J. Hund, Samuel Sossalla, Lars S. Maier, Stefan Wagner
Journal: Circulation (2022)
CTRR-ncRNA: A Knowledgebase for Cancer Therapy Resistance and Recurrence Associated Non-Coding RNAs
Authors: Tong Tang, Xingyun Liu, Rongrong Wu, Li Shen, Shumin Ren, Bairong Shen
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract Cancer therapy resistance and recurrence (CTRR) are the dominant causes of death in cancer patients. Recent studies have indicated that non-coding RNAs (ncRNAs) can not only reverse the resistance to cancer therapy but also are crucial biomarkers for the evaluation and prediction of CTRR. Herein, we developed CTRR-ncRNA, a knowledgebase of CTRR-associated ncRNAs, aiming to provide an accurate and comprehensive resource for research involving the association between CTRR and ncRNAs. Compared to most of the existing cancer databases, CTRR-ncRNA is focused on the clinical characterization of cancers, including cancer subtypes, as well as survival outcomes and responses to personalized therapy of cancer patients. Information pertaining to biomarker ncRNAs has also been documented for the development of personalized CTRR prediction. A user-friendly interface and several functional modules have been incorporated into the database. Based on the preliminary analysis of genotype–phenotype relationships, universal ncRNAs have been found to be potential biomarkers for CTRR. The CTRR-ncRNA is a translation-oriented knowledgebase and it provides a valuable resource for mechanistic investigations and explainable artificial intelligence-based modeling. CTRR-ncRNA is freely available to the public at http://ctrr.bioinf.org.cn/.
Predictive uncertainty estimation for out-of-distribution detection in digital pathology
Authors: Jasper Linmans, Stefan Elfwing, Jeroen van der Laak, Geert Litjens
Journal: Medical Image Analysis (2022)

Machine learning model deployment in clinical practice demands real-time risk assessment to identify situations in which the model is uncertain. Once deployed, models should be accurate for classes seen during training while providing informative estimates of uncertainty to flag abnormalities and unseen classes for further analysis. Although recent developments in uncertainty estimation have resulted in an increasing number of methods, a rigorous empirical evaluation of their performance on large-scale digital pathology datasets is lacking. This work provides a benchmark for evaluating prevalent methods on multiple datasets by comparing the uncertainty estimates on both in-distribution and realistic near and far out-of-distribution (OOD) data on a whole-slide level. To this end, we aggregate uncertainty values from patch-based classifiers to whole-slide level uncertainty scores. We show that results found in classical computer vision benchmarks do not always translate to the medical imaging setting. Specifically, we demonstrate that deep ensembles perform best at detecting far-OOD data but can be outperformed on a more challenging near-OOD detection task by multi-head ensembles trained for optimal ensemble diversity. Furthermore, we demonstrate the harmful impact OOD data can have on the performance of deployed machine learning models. Overall, we show that uncertainty estimates can be used to discriminate in-distribution from OOD data with high AUC scores. Still, model deployment might require careful tuning based on prior knowledge of prospective OOD data.
FDG PET/CT in Immune-Related Arthritis in a Patient Treated With Nivolumab
Authors: Mohadeseh Bayat, Abtin Doroudinia, Mehrdad Bakhshayesh Karam, Payam Mehrian
Journal: Clinical Nuclear Medicine (2022)

Immune checkpoint inhibitors are a new and different treatment option in many of solid tumors, but with many recognized immune-related adverse side effects. In this interesting image, we are presenting a 56-year-old woman with primary malignant melanoma who underwent nivolumab therapy for 5 months, and a posttreatment whole-body FDG PET/CT scan for treatment response evaluation demonstrated increased metabolic activity in the entire major joints of the upper and lower extremities. This was a new finding compared with previous FDG PET/CT scan and was interpreted as an immune-related arthritis complication.
Complete Metabolic Response in Adenocarcinoma Lung With Lymphangitic Carcinomatosis
Authors: Harish Goyal, Sai Kishore, Prasanth Ganesan, Dhanapathi Halanaik
Journal: Clinical Nuclear Medicine (2022)

Pulmonary lymphangitic carcinomatosis refers to the tumor spread into the lymphatic system of the lungs and is considered a poor prognostic marker. We present an interesting case of adenocarcinoma of right lung evaluated with 18 F-FDG PET/CT for baseline staging, with extensive bilateral lung involvement and lymphangitic carcinomatosis pattern. Subsequently, the patient received 3 cycles of carboplatin- and pemetrexed-based chemotherapy regimen along with oral ceritinib. Complete metabolic response and significant reduction in size of the primary lung lesion was noted on response evaluation with 18 F-FDG PET/CT, which is a rare phenomenon.
Nocardia Infection With Adrenal Gland Abscess Mimicking Metastatic Lung Cancer on FDG PET/CT
Authors: Selin Kesim, Kevser Oksuzoglu, Salih Ozguven
Journal: Clinical Nuclear Medicine (2022)

We present FDG PET/CT findings of a human immunodeficiency virus-positive patient suspicious for lung cancer with a solitary metastasis to the adrenal gland. Wedge resection of the pulmonary nodules revealed Nocardia infection and a repeat FDG PET/CT imaging after the antibiotic treatment demonstrated complete metabolic response of the adrenal lesion and pulmonary nodules. It should be kept in mind that nocardiosis may present with FDG-avid lesions masquerading as malignancies in immunocompromised patients.
18F-MFBG PET/CT Is an Effective Alternative of 68Ga-DOTATATE PET/CT in the Evaluation of Metastatic Pheochromocytoma and Paraganglioma
Authors: Peipei Wang, Tuo Li, Yuying Cui, Hongming Zhuang, Fang Li, Anli Tong, Hongli Jing
Journal: Clinical Nuclear Medicine (2022)

Purpose The current guidelines state that the functional imaging choice in the evaluation of metastatic pheochromocytoma and paraganglioma (PPGL) is 68 Ga-DOTATATE PET/CT. 18 F–meta-fluorobenzylguanidine ( 18 F-MFBG) is a new PET tracer and an analog of meta-iodobenzylguanidine (MIBG). This study aimed to compare 18 F-MFBG and 68 Ga-DOTATATE PET/CT in patients with metastatic PPGL. Patients and Methods Twenty-eight patients with known metastatic PPGL were prospectively recruited for this study. All patients underwent both 18 F-MFBG and 68 Ga-DOTATATE PET/CT studies within 1 week. Lesion numbers detected were compared between these 2 studies. Results 18 F-MFBG PET/CT was positive for detecting metastases in all patients, whereas positive results of 68 Ga-DOTATATE PET/CT were in 27 (96.4%) patients. A total of 686 foci of metastatic lesions were detected by both 18 F-MFBG and 68 Ga-DOTATATE imaging. In addition, 33 foci of abnormal activity were only detected by 18 F-MFBG, whereas 16 foci were only shown on 68 Ga-DOTATATE PET/CT. Conclusions Our data suggest that 18 F-MFBG PET/CT is an effective imaging method in the evaluation of metastatic PPGL and could be alternative of 68 Ga-DOTATATE PET/CT in this clinical setting.
A “Leopard Man” Aspect on 18F-FDG PET/CT Revealing a VEXAS Syndrome
Authors: Alexandre Fagart, Thomas Quemeneur, Guillaume Collet, Franck Demailly, Clementine Rousselin
Journal: Clinical Nuclear Medicine (2022)

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset autoinflammatory disease caused by somatic UBA1 mutations first described in 2020. Most of these patients met clinical criteria for an inflammatory syndrome (relapsing polychondritis, Sweet syndrome, polyarteritis nodosa, or giant-cell arteritis) or a hematologic condition (myelodysplastic syndrome or multiple myeloma) or both. We described here an FDG PET/CT "leopard man" appearance, with abnormal marrow recruitment the findings, in a 70-year-old man diagnosed with a VEXAS syndrome.
Warthin-Like Papillary Thyroid Microcarcinoma With Coincidental Ipsilateral Warthin Tumor of the Parotid Gland Detected on 131I-SPECT/US and 18F-PET/US Fusion Imaging
Authors: Anke Werner, Martin Freesmeyer, Claudia Bensch, Markus Eszlinger, Philipp Seifert
Journal: Clinical Nuclear Medicine (2022)

A 66-year-old woman was referred with an incidental finding of a bilateral papillary thyroid microcarcinoma after thyroidectomy. On the right side, a Warthin-like variant was observed. After radioiodine therapy, whole-body scan revealed an unclear iodine uptake on the right-sided neck. For further clarification, 131 I-SPECT/US and 18 F-PET/US fusion imaging were performed, unambiguously revealing iodine and glucose uptake within a hypoechoic lesion located in the parenchyma of the right parotid gland. Surgical excision confirmed a Warthin tumor ipsilateral to the Warthin-like variant of the papillary thyroid microcarcinoma. Because the extensive imaging, targeted minimal-invasive surgery was possible.
Similar Findings on 68Ga-Pentixafor PET/CT and 18F-FDG PET/CT in a Patient With Widespread Metastatic Hepatic Neuroendocrine Carcinoma
Authors: Maoxue Deng, Qiaoqiao Shu, Mei Hu, Yue Chen, Liang Cai
Journal: Clinical Nuclear Medicine (2022)

A patient with suspected malignant tumor underwent 18 F-FDG PET/CT. Based on the findings, the patient was suspected of having multiple myeloma. Then the patient underwent 68 Ga-pentixafor PET/CT, which showed similar results to 18 F-FDG PET/CT. Finally, the patient was eventually diagnosed with neuroendocrine carcinoma.